USP22 controls necroptosis by regulating receptor‐interacting protein kinase 3 ubiquitination
| Autor: | Petra Beli, Lisa Kowald, Jens Roedig, Rebekka Karlowitz, Behnaz Ahangarian Abhari, Sjoerd J L van Wijk, Heiko Roedig, Simone Fulda, Thomas Juretschke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
RIPK1 Necroptosis Apoptosis ubiquitin hydrolase Biochemistry Article Deubiquitinating enzyme 03 medical and health sciences Necrosis 0302 clinical medicine Ubiquitin Genetics cancer Humans post‐translational modifications Protein kinase A Molecular Biology 030304 developmental biology 0303 health sciences biology Chemistry NF-kappa B Ubiquitination Post-translational Modifications Proteolysis & Proteomics Articles Cell biology Histone Receptor-Interacting Protein Serine-Threonine Kinases mixed lineage kinase domain‐like biology.protein Autophagy & Cell Death Ubiquitin Thiolesterase 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | EMBO Reports |
| ISSN: | 1469-3178 1469-221X |
| Popis: | Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin‐specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of mono‐ubiquitination from histones H2A and H2B, thereby regulating gene transcription. However, novel roles for USP22 have emerged recently, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in human tumor cell lines. Loss of USP22 expression significantly delays TNFα/Smac mimetic/zVAD.fmk (TBZ)‐induced necroptosis, without affecting TNFα‐mediated NF‐κB activation or extrinsic apoptosis. Ubiquitin remnant profiling identified receptor‐interacting protein kinase 3 (RIPK3) lysines 42, 351, and 518 as novel, USP22‐regulated ubiquitination sites during necroptosis. Importantly, mutation of RIPK3 K518 reduced necroptosis‐associated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of RIPK3 ubiquitination as crucial regulator of necroptotic cell death. Ubiquitin‐specific protease 22 (USP22) controls necroptotic cell death by regulating RIPK3 phosphorylation and RIPK3 K518 ubiquitination in human tumor cell lines. |
| Databáze: | OpenAIRE |
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